Abstract Topical commercial formulations containing diclofenac (DC) were submitted to photostability tests, according to the international rules, showing a clear degradation of the drug. The degradation process was monitored by applying the multivariate curve resolution technique to the UV spectral data from samples exposed to stressing irradiation. This method was able to estimate the number of components evolved as well as to draw their spectra and concentration profiles. Three photoproducts (PhPs) were resolved by the analysis of photodegradation kinetics, according to two consecutive reactions with a mechanism postulated as DC>PhP1>PhP2 and PhP3. Photodegradation rate of DC in gel was found to be very fast, with a residual content of 90% only after 3.90min under a radiant exposure of 450Wm−2. Because of a very slow skin uptake of DC, a prolonged time of exposure to light could lead to a significant decrease of drug available or the uptake of undesired photoproducts. New gel formulations were designed to increase the photostability of DC by incorporating chemical light-absorbers or entrapping the drug into cyclodextrin. Drug photostability resulted increased significantly in comparison with that of the commercial formulations. The gel containing the light-absorbers such as octisilate, octyl methoxycinnamate and a combination thereof showed a residual DC of 90% up to 12.22min, 13.75min and 15.71min, respectively, under the same irradiation power. The best results were obtained by incorporating the drug in β-cyclodextrin with a degradation of 10% after 25.01min of light exposure.